Growth and differentiation of B-cells to plasma cells involve regulation by a variety of interleukins. Development of plasma cell neoplasias (myelomas) requires, in addition, activation of several oncogenes. Rearrangement of the interleukin 6 (IL-6) gene, and its subsequent constitutive expression in a myeloma, led to the suggestion that IL-6 may be involved in development of certain myelomas by an autocrine growth mechanism. Therefore, we analyzed genomic DNA from a collection of early generation myelomas to determine whether any of these had rearrangements in the IL-6 gene. A total of 55 myeloma DNAs were analyzed, with 40 of these from myelomas at generation 3 or earlier. Southern analysis of DNA cut with EcoRI and probed with an IL-6 probe would detect rearrangements at both the 5' or 3' ends of the gene. No differences were found in the genomic IL-6 DNA in the myelomas compared with that in the germline DNA. Thus it is unlikely that continuous deregulated expression of IL-6 due to a gene rearrangement plays a major role in generation of myelomas in the mouse. IAP genes expressed in LPS stimulated B-cells of the BALB/c mouse have been shown to represent a restricted set of elements which can be distinguished by specific sequences in the R regions of the LTR (see Kuff Annual Report 91).